{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T06:36:44Z","timestamp":1792478204921,"version":"4.5.0"},"reference-count":52,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"3","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China: National Science Foundation for Excellent Young Scholars","award":["32122052"],"award-info":[{"award-number":["32122052"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Commun"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Understanding how the tumor microenvironment is shaped by various factors is important for the development of new therapeutic strategies. Tumor cells often undergo spontaneous apoptotic cell death in tumor microenvironment, these apoptotic cells are histologically co\u2010localized with immunosuppressive macrophages. However, the mechanism by which tumor cell apoptosis modulates macrophage polarization is not fully understood. In this study, we aimed to explore the tumor promoting effects of apoptotic tumor cells and the signal pathways involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Apoptotic cells and macrophages in tumors were detected by immunohistochemical staining. Morphological analysis was performed with Giemsa staining. Lipids generated from apoptotic cells were detected by liquid chromatography\u2010mass spectrometry. Phosphatidylserine\u2010containing liposomes were prepared to mimic apoptotic cells. The expression of protein was determined by real\u2010time PCR, immunohistochemistry enzyme\u2010linked immunosorbent assay and Western blotting. Mouse malignant ascites and subcutaneous tumor models were designed for in vivo analysis. Transgenic mice with specific genes knocked out and inhibitors specific to certain proteins were used for the mechanistic studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">The location and the number of apoptotic cells were correlated with that of macrophages in several types of carcinomas. Phosphatidylserine, a lipid molecule generated in apoptotic cells, induced polarization and accumulation of M2\u2010like macrophages in vivo and in vitro. Moreover, sustained administration of phosphoserine promoted tumor growth in the malignant ascites and subcutaneous tumor models. Further analyses suggested that phosphoserine induced a M2\u2010like phenotype in macrophages, which was related to the activation of phosphoserine receptors including T\u2010cell immunoglobin mucin 4 (TIM4) and the FAK\u2010SRC\u2010STAT3 signaling pathway as well as elevated the expression of the histone demethylase Jumonji domain\u2010containing protein 3 (JMJD3). Administration of specific inhibitors of these pathways could reduce tumor progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">This study suggest that apoptotic cell\u2010generated phosphoserine might be a notable signal for immunosuppressive macrophages in tumors, and the related pathways might be potential therapeutic targets for cancer therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cac2.12272","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T04:40:27Z","timestamp":1645504827000},"page":"205-222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Phosphatidylserine released from apoptotic cells in tumor induces M2\u2010like macrophage polarization through the PSR\u2010STAT3\u2010JMJD3 axis"],"prefix":"10.34133","volume":"42","author":[{"given":"Xiao","family":"Liang","sequence":"first","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]},{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Luo","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Shao","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Yun","family":"Yang","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Tong","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui\u2010Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Tong","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Jun","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yi","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Quan","family":"Wei","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6513-6422","authenticated-orcid":false,"given":"Xia\u2010Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["Chengdu, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-018-0007-y"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-013-0367-7"},{"issue":"11","key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S1471-4906(02)02302-5","article-title":"Macrophage polarization: tumor\u2010associated macrophages as a paradigm for polarized M2 mononuclear phagocytes","volume":"23","author":"Mantovani A","year":"2002","unstructured":"Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor\u2010associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23((11)):549\u201355.","journal-title":"Trends Immunol"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-0012"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.03.014"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0127-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053010"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2792"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.58"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.12.059"},{"issue":"3","key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s10555-006-9001-7","article-title":"Role of tumor\u2010associated macrophages in tumor progression and invasion","volume":"25","author":"Mantovani A","year":"2006","unstructured":"Mantovani A, Schioppa T, Porta C, Allavena P, Sica A. Role of tumor\u2010associated macrophages in tumor progression and invasion. Cancer Metastasis Rev. 2006;25((3)):315.","journal-title":"Cancer Metastasis Rev"},{"issue":"15","key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"4391","DOI":"10.1158\/1078-0432.CCR-09-0489","article-title":"HPV16 Tumor Associated Macrophages Suppress Antitumor T Cell Responses","volume":"15","author":"Lepique AP","year":"2009","unstructured":"Lepique AP, Daghastanli KRP, Cuccovia IM, Villa LL. HPV16 Tumor Associated Macrophages Suppress Antitumor T Cell Responses. Clin Cancer Res. 2009;15((15)):4391\u2013400.","journal-title":"Clin Cancer Res"},{"issue":"6","key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1093\/jmcb\/mjv022","article-title":"The histone H3 lysine\u201027 demethylase Jmjd3 plays a critical role in specific regulation of Th17 cell differentiation","volume":"7","author":"Liu Z","year":"2015","unstructured":"Liu Z, Cao W, Xu L, Chen X, Zhan Y, Yang Q, et\u00a0al. The histone H3 lysine\u201027 demethylase Jmjd3 plays a critical role in specific regulation of Th17 cell differentiation. J Mol Cell Biol. 2015;7((6)):505\u201316.","journal-title":"J Mol Cell Biol"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.9"},{"issue":"11","key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1158\/1535-7163.MCT-13-0040","article-title":"UNC569, a novel small\u2010molecule mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo","volume":"12","author":"Christoph S","year":"2013","unstructured":"Christoph S, DeRyckere D, Schlegel J, Frazer JK, Batchelor LA, Trakhimets AY, et\u00a0al. UNC569, a novel small\u2010molecule mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo. Mol Cancer Ther. 2013;12((11)):2367\u201377.","journal-title":"Mol Cancer Ther"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-018-2631-7"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609757104"},{"issue":"3","key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1084\/jem.180.3.945","article-title":"Isolation of a nitric oxide inhibitor from mammary tumor cells and its characterization as phosphatidyl serine","volume":"180","author":"Calderon C","year":"1994","unstructured":"Calderon C, Huang Z\u2010H, Gage DA, Sotomayor EM, Lopez DM. Isolation of a nitric oxide inhibitor from mammary tumor cells and its characterization as phosphatidyl serine. J Exp Med. 1994;180((3)):945\u201358.","journal-title":"J Exp Med"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1401s83"},{"issue":"19","key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"7022","DOI":"10.1158\/0008-5472.CAN-04-1449","article-title":"A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors","volume":"64","author":"Wyckoff J","year":"2004","unstructured":"Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, et\u00a0al. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 2004;64((19)):7022\u20139.","journal-title":"Cancer Res"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13490"},{"issue":"1","key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-021-01313-x","article-title":"Non\u2010coding RNAs regulation of macrophage polarization in cancer","volume":"20","author":"Mohapatra S","year":"2021","unstructured":"Mohapatra S, Pioppini C, Ozpolat B, Calin GA. Non\u2010coding RNAs regulation of macrophage polarization in cancer. Mol Cancer. 2021;20((1)):1\u201315.","journal-title":"Mol Cancer"},{"issue":"3","key":"e_1_3_2_24_2","first-page":"1100","article-title":"Macrophage arginase promotes tumor cell growth and suppresses nitric oxide\u2010mediated tumor cytotoxicity","volume":"61","author":"Chang CI","year":"2001","unstructured":"Chang CI, Liao JC, Kuo L. Macrophage arginase promotes tumor cell growth and suppresses nitric oxide\u2010mediated tumor cytotoxicity. Cancer Res. 2001;61((3)):1100\u20136.","journal-title":"Cancer Res"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-162404"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(95)00072-I"},{"issue":"7","key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.4049\/jimmunol.148.7.2207","article-title":"Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages","volume":"148","author":"Fadok VA","year":"1992","unstructured":"Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol. 1992;148((7)):2207\u201316.","journal-title":"J Immunol"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2011.28"},{"issue":"6","key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.immuni.2007.11.011","article-title":"TIM\u20101 and TIM\u20104 Glycoproteins Bind Phosphatidylserine and Mediate Uptake of Apoptotic Cells","volume":"27","author":"Kobayashi N","year":"2007","unstructured":"Kobayashi N, Karisola P, Pe\u00f1acruz V, Dorfman DM, Jinushi M, Umetsu SE, et\u00a0al. TIM\u20101 and TIM\u20104 Glycoproteins Bind Phosphatidylserine and Mediate Uptake of Apoptotic Cells. Immunity. 2007;27((6)):927.","journal-title":"Immunity"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402242"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3847"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.08.030"},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.3389\/fimmu.2018.02033","article-title":"Aryl Hydrocarbon Receptor Promotes IL\u201010 Expression in Inflammatory Macrophages Through Src\u2010STAT3 Signaling Pathway","volume":"9","author":"Zhu J","year":"2018","unstructured":"Zhu J, Luo L, Tian L, Yin S, Ma X, Cheng S, et\u00a0al. Aryl Hydrocarbon Receptor Promotes IL\u201010 Expression in Inflammatory Macrophages Through Src\u2010STAT3 Signaling Pathway. Front Immunol. 2018;9:2033.","journal-title":"Front Immunol"},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/512926","article-title":"The role of Src kinase in macrophage\u2010mediated inflammatory responses","volume":"2012","author":"Byeon SE","year":"2012","unstructured":"Byeon SE, Yi YS, Oh J, Yoo BC, Hong S, Cho JY. The role of Src kinase in macrophage\u2010mediated inflammatory responses. Mediators Inflamm. 2012;2012:512926.","journal-title":"Mediators Inflamm"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","DOI":"10.1038\/srep22363","article-title":"Hydrogen Sulfide Recruits Macrophage Migration by Integrin \u03b21\u2010Src\u2010FAK\/Pyk2\u2010Rac Pathway in Myocardial Infarction","volume":"6","author":"Miao L","year":"2016","unstructured":"Miao L, Xin X, Xin H, Shen X, Zhu YZ. Hydrogen Sulfide Recruits Macrophage Migration by Integrin \u03b21\u2010Src\u2010FAK\/Pyk2\u2010Rac Pathway in Myocardial Infarction. Sci Rep. 2016;6:22363.","journal-title":"Sci Rep"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-207522"},{"issue":"10","key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/ni.1920","article-title":"The Jmjd3\u2010Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection","volume":"11","author":"Satoh T","year":"2010","unstructured":"Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, et\u00a0al. The Jmjd3\u2010Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol. 2010;11((10)):936.","journal-title":"Nat Immunol"},{"issue":"6","key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1093\/jmcb\/mjv022","article-title":"The histone H3 lysine\u201027 demethylase Jmjd3 plays a critical role in specific regulation of Th17 cell differentiation","volume":"7","author":"Liu Z","year":"2015","unstructured":"Liu Z, Cao W, Xu L, Chen X, Zhan Y, Yang Q, et\u00a0al. The histone H3 lysine\u201027 demethylase Jmjd3 plays a critical role in specific regulation of Th17 cell differentiation. J Mol Cell Biol. 2015;7((6)):505.","journal-title":"J Mol Cell Biol"},{"issue":"7163","key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nature06145","article-title":"UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development","volume":"449","author":"Agger K","year":"2007","unstructured":"Agger K, Cloos PA, Christensen J, Pasini D, Rose S, Rappsilber J, et\u00a0al. UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature. 2007;449((7163)):731\u20134.","journal-title":"Nature"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-1367"},{"issue":"13","key":"e_1_3_2_41_2","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1158\/0008-5472.CAN-17-2158","article-title":"Inflammatory breast cancer promotes development of M2 tumor\u2010associated macrophages and cancer mesenchymal cells through a complex chemokine network","volume":"79","author":"Valeta\u2010Magara A","year":"2019","unstructured":"Valeta\u2010Magara A, Gadi A, Volta V, Walters B, Arju R, Giashuddin S, et\u00a0al. Inflammatory breast cancer promotes development of M2 tumor\u2010associated macrophages and cancer mesenchymal cells through a complex chemokine network. Cancer Res. 2019;79((13)):3360\u201071.","journal-title":"Cancer Res"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170681"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76375"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-1106"},{"issue":"11","key":"e_1_3_2_45_2","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1096\/fj.06-7815com","article-title":"Apoptotic cells induce arginase II in macrophages, thereby attenuating NO production","volume":"21","author":"Johann AM","year":"2007","unstructured":"Johann AM, Barra V, Kuhn AM, Weigert A, Von KA, Br\u00fcne B. Apoptotic cells induce arginase II in macrophages, thereby attenuating NO production. FASEB J. 2007;21((11)):2704\u201312.","journal-title":"FASEB J"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2385"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170681"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)89189-X"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200108080"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/35011084"},{"issue":"9","key":"e_1_3_2_51_2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0107063","article-title":"Induction of murine macrophage M2 polarization by cigarette smoke extract via the JAK2\/STAT3 pathway","volume":"9","author":"Yuan F","year":"2014","unstructured":"Yuan F, Fu X, Shi H, Chen G, Dong P, Zhang W. Induction of murine macrophage M2 polarization by cigarette smoke extract via the JAK2\/STAT3 pathway. PLoS One. 2014;9((9)):e107063.","journal-title":"PLoS One"},{"issue":"10","key":"e_1_3_2_52_2","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1111\/j.1349-7006.2010.01652.x","article-title":"Involvement of M2\u2010polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via Stat3 activation","volume":"101","author":"Takaishi K","year":"2010","unstructured":"Takaishi K, Komohara Y, Tashiro H, Ohtake H, Nakagawa T, Katabuchi H, et\u00a0al. Involvement of M2\u2010polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via Stat3 activation. Cancer Sci. 2010;101((10)):2128\u201336.","journal-title":"Cancer Sci"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-04-217620"}],"container-title":["Cancer Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cac2.12272","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cac2.12272","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.1002\/cac2.12272","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T08:52:30Z","timestamp":1773823950000},"score":1,"resource":{"primary":{"URL":"https:\/\/spj.science.org\/doi\/10.1002\/cac2.12272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,22]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1002\/cac2.12272"],"URL":"https:\/\/doi.org\/10.1002\/cac2.12272","relation":{},"ISSN":["2523-3548"],"issn-type":[{"value":"2523-3548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,22]]},"assertion":[{"value":"2021-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}